We intend to study two separate aspects of the molecular biology of avian retroviruses. Several groups have recently reported that avian leukosis viruses (ALVs) produce lymphoid leukosis after a ong latent period by eventually integrating next to and activating the cellular myc gene. Other very closely related ALVs however appear unable to produce leukosis but instead produce a proliferative disease of the long bones of the legs termed osteopetrosis. We intend to create in vitro recombinant viruses using DNA cloning methods to determine what region of the viral DNA is viruses using DNA cloning methods to determine what region of the viral DNA is responsible for this altered disease spectrum. Our second project relates to the stability of ALV proviruses within the cell. We have obtained preliminary evidence suggesting proviruses may have the capacity to both excise and integrate during extended passage of cloned cells in culture. We intend to examine the sites into which the provirus will integrate and the sites from which the provirus has excised using DNA cloning techniques to define more precisely the nature of this provirus instability. We hope to be able to extend the similarity between retroviruses and transposable genetic elements beyond the previously noted structural features into function.